Hantzsch reaction using copper nitrate hydroxide-containing mesoporous silica nanoparticle with C3N4 framework as a novel powerful and reusable catalyst

Copper nitrate hydroxide (CNH)-containing mesoporous silica nanoparticle (MSN) with g-C3N4 framework (MSN/C3N4/CNH) was fabricated via a four-step hydrothermal synthesis method. Functionalized MSN-based C3N4 was prepared, decorated with CNH, and identified by different physicochemical techniques such as FT-IR, XRD, SEM, EDX, and STA analyses. Then, MSN/C3N4/CNH composite was utilized as a robust catalyst for the fast fabrication of biologically active polyhydroquinoline derivatives with high yields between 88 and 97% via Hantzsch reaction under mild reaction conditions and short reaction time (within 15 min) owing to synergistic influence of Lewis acid and base sites. Moreover, MSN/C3N4/CNH can be straightforwardly recovered and used up to six reaction cycles without a conspicuous decrease in efficiency.

www.nature.com/scientificreports/ specific surface area, excellent mechanical strength, high conductivity, and fascinating physicochemical features. Among these, graphitic carbon nitride (g-C 3 N 4 ) as a free metals material is especially of attention, owing to its unique crystal structure, nontoxic, cost-effectiveness, high thermal and chemical stability, and resistance to acidic and basic conditions 48 . C 3 N 4 has a stacked two-dimensional structure and can be synthesized easily from low-cost precursors such as urea, thiourea, melamine, and cyanamide via pyrolysis. Owing to its promising features, g-C 3 N 4 and its composites are applied in a variety of photocatalytic applications 49 . So far, g-C 3 N 4 has been utilized as a catalyst or catalyst support in various organic reactions [50][51][52][53][54][55] . However, the practical application of g-C 3 N 4 is limited by its low surface area, insufficient light absorption, reduction potential, inappropriate rapid recombination, and large diffusion resistance of charges. The g-C 3 N 4 can enhance the surface area, promote charge transfer and mass diffusion through nanostructure materials design.
Copper hydroxide nitrate, [Cu 2 (OH) 3 NO 3 ], is a basic copper(II) salt with a layered structure, that have applications in vehicle airbags, catalyst, and ion exchangers [56][57][58][59][60] . [Cu 2 (OH) 3 NO 3 ] exists as two structurally related dimorphs, a synthetic metastable monoclinic phase and a natural orthorhombic phase occurring in the mineral gerhardtite. The structure can be observed as layers of copper octahedra stacked with each other. The Cu octahedral form layers of stoichiometry [Cu 2 (OH) 3 ] + , and NO 3 − ions stand in between the positive layers for charge balance, which are linked to the hydroxyl groups via hydrogen bonding belonging to the copper octahedra layers.
In this study, g-C 3 N 4 /MSN was fabricated and utilized as a support to load copper nitrate hydroxide (CNH) (Cu 2 (OH) 3 NO 3 ) and emerged as a competent heterogeneous nanocatalyst for the Hantzsch reaction.

Experimental
Preparation of MSN. 0.2 g of glucose was dissolved in 90 mL of ethanol. Then, 4 mL of TEOS (as the silica source) and 6 mL of distilled water were added to the above solution and subsequently stirred at room temperature for 12 h. The solid was separated by centrifuge and washed with distilled water and ethanol, respectively. The obtained white solid calcined at 550 °C for 6 to the production of porous silica hollow sphere. , and aldehyde (1 mmol) was stirred at 50 °C, as monitored via TLC (ethyl acetate/n-hexane 50:50) for a complete reaction. Then, 10 mL of solvent (warm ethanol) was added to the mixture and MSN/C 3 N 4 /CNH was separated via filtration. The underlying solution was heated to boiling temperature and then a piece of ice was added to precipitate the desired crystalline product. The solvent was vaporized and ethanol was utilized to crystallize the resultant product. Then, the recovered MSN/C 3 N 4 /CNH was reused in six runs under similar conditions as the first run to represent the recyclability and stability of the prepared catalyst.

Results and discussion
Synthesis of MSN/C 3 N 4 /CNH. An adequate amount of TEOS as silica precursor was added to a mixture of glucose as sacrificial template and carbon source and ethanol as a solvent. After calcination at elevated temperature, glucose was removed. MSN/C 3 N 4 was fabricated via calcination technique onto MSN surface using urea as a precursor. MSN/C 3 N 4 was applied as support material to anchor CNH to afford MSN/C 3 N 4 /CNH (Fig. 1).
Characterization of synthesized compounds. FTIR spectra of silica-glucose sample without calcination (a), MSN (b), MSN/C 3 N 4 (c), and MSN/C 3 N 4 /CNH (d) are revealed in Fig. 2. The spectrum of non-calcined sample showed the board peak at 1087 cm −1 (Si-O-Si groups) and the band at 2923 cm −1 (C-H bonds). After calcination, the absorption peak of C-H bonds disappeared due to decomposition of templet, while the peaks of silanol and siloxane remained. In the spectrum of MSN, the peak appeared at 3429 cm −1 belonged to the stretching vibration of O-H; the absorption bands at 1082 and 810 cm −1 assigned the asymmetric and symmetric stretching vibrations of Si-O-Si, respectively. In the spectrum of MSN/C 3 N 4 , the broad band in the range of 3500-3000 cm −1 indicates the presence of N-H stretching vibration of the terminal amino group in g-C 3 N 4 . The peak around 1640 cm −1 contributed to the stretching mode of C=N bonds. The intense bands observed at 1560, 1427, 1320, and 1243 cm −1 were due to the presence of C-N stretching of tri-s-triazine. The band around 800 cm −1 reveals out-of-plane bending vibration of triazinecycle. In the spectrum of MSN/C 3 N 4 /CNH, the peak at 3427 cm −1 corresponds to the stretching vibration of the O-H of molecular water, and the band at 1662 cm −1 is owing to the bending mode of H 2 O molecules. The presence of NO 3 − in MSN/C 3 N 4 /CNH is evidenced by the vibration bands that appeared from middle to lower wavenumbers, confirming the presence of mono-or polydentate nitrate ligands. The sharp absorption bands at 1052 and 1393 cm −1 revealing for copper nitrate hydroxide. The bands at 1384 cm −1 (strong) and 872 cm −1 are related to NO 3 groups. The absorption band at 1052 cm −1 was assigned to the bending vibration of Cu-O-H. Besides, the peaks in the range of 700-500 cm −1 were attributed to the presence of metal-oxygen bonds. www.nature.com/scientificreports/ The XRD pattern of MSN (a) and simulated CNH, and MSN/C 3 N 4 /CNH (b) was described in Fig. 3. The XRD pattern of MSN exhibits a broad diffraction peak at approximately 22° which is characteristic of amorphous silica. In the XRD pattern of MSN/C 3 N 4 /CNH, all diffraction peaks can be well indexed to a pure phase of CNH with a monoclinic structure (JCPDS No. 74-1749). The intensive and clear peaks confirmed that MSN/C 3 N 4 /CNH nanocomposite is well crystallized. No peaks could be appeared for the impurities including Cu, CuO, Cu 2 O, Cu(OH) 2 , or Cu(NO 3 ) 2 , demonstrating the high purity of MSN/C 3 N 4 /CNH nanocomposite. Furthermore, the peak at 27.5°, which corresponded to the (002) plane, was designated graphitic interlayer stacking structure of g-C 3 N 4 .
In FE-SEM image of MSN/C 3 N 4 /CNH composite, spherical nanoparticles were visible, distributed uniformly over the support material with some agglomeration (Fig. 4).
The average particle size was found to be around 22-38 nm. The energy dispersive X-ray (EDS) analysis proves the existence of Cu along with Si, N, C, and O elements in MSN/C 3 N 4 /CNH composite (Fig. 5).
The thermal stability of MSN/C 3 N 4 /CNH nanocomposite was examined by the simultaneous thermal analysis (STA) under a nitrogen atmosphere (Fig. 6). The initial mass loss at 125 °C is due to the evaporation of adsorbed H 2 O molecules. Between 220 and 280 °C, a mass loss is attributed to Cu 2 (OH) 3 NO 3 decomposing into CuO and the removal of H 2 O, NO 2 , and O 2 . There is a weight loss between 390 and 520 °C, which is assigned to the combustion of g-C 3 N 4 .
Catalytic activity test. The catalytic application of MSN/C 3 N 4 /CNH is tested in the Hantzsch reaction under diverse conditions ( Table 1). The results illustrated that the reaction progress is highly affected by the     entries 13 and 14). The reactions of various aldehydes possessing either electron-donating or electron-withdrawing substituents with ethyl acetoacetate, dimedone, and ammonium acetate in the presence of a catalytic amount (10 mg) of MSN/ C 3 N 4 /CNH afforded high yields of the corresponding polyhydroquinoline derivatives (88-97%) in a short time under the optimized model reaction conditions ( Table 2). The results demonstrate that the type and position of the substituent possess no substantial influence on the activity of MSN/C 3 N 4 /CNH catalyst. The results confirm the outstanding efficiency of MSN/C 3 N 4 /CNH for the conversion of an extensive range of aldehydes. www.nature.com/scientificreports/ The proposed mechanism for the synthesis of polyhydroquinoline compounds via the Hantzsch reaction is depicted in Fig. 7. As CNH was comprised of copper hydroxide, Cu-OH bonds would exist, and Cu-OH cluster has been considered an active site for the construction of polyhydroquinoline. MSN/C 3 N 4 /CNH catalyst has both Lewis acidic sites (Cu) and basic sites (OH and C 3 N 4 ), hence it is an efficient heterogeneous catalyst for the Hantzsch reaction. According to literature, Cu-OH would firstly activate the carbonyl group of aldehyde by interacting oxygen with Cu metal. The role of MSN/C 3 N 4 /CNH comes in steps 1 and 4, in which catalyzes the Knoevenagel type coupling of aldehydes with 1,3-dicarbonyl compounds and in steps 3 and 6 where it catalyzes

Reusability of MSN/C 3 N 4 /CNH.
After demonstrating the activity of MSN/C 3 N 4 /CNH catalyst for the various reactions, its reusability was examined in the model reaction. In each cycle, MSN/C 3 N 4 /CNH was straightforwardly recovered, washed with ethanol, and dried at 60 °C. The reaction was repeated and the results exhibited that MSN/C 3 N 4 /CNH could be reused up to six times with a slight reduction in the catalytic activity (Fig. 8). This observation confirms the high recycling efficiency of MSN/C 3 N 4 /CNH, which is a noteworthy property from economic and environmental points of view.

Comparison of MSN/C 3 N 4 /CNH with previously reported catalysts for the Hantzsch reaction.
The performance of the MSN/C 3 N 4 /CNH catalyst was compared with that of catalysts reported in literature for the unsymmetrical Hantzsch reaction (Table 3). It is found that MSN/C 3 N 4 /CNH catalyst is superior to the majority of the reported catalysts in terms of cost-effectiveness, simplicity, short reaction time, amount of catalyst, type of solvent, and mild conditions.

Conclusions
CNH grown on MSN/C 3 N 4 surface was fabricated and utilized as a recoverable and powerful nanocatalyst for the one-pot construction of polyhydroquinolines in 15 min with a quantity of catalyst 10 mg at 50 °C under solventfree conditions. The exceptional performance of MSN/C 3 N 4 /CNH catalyst can be attributed to the acid-base sites synergistic catalysis present in the catalyst. MSN/C 3 N 4 /CNH was straightforwardly recovered and reused six times with a slight reduction in the catalytic activity. The benefits of using MSN/C 3 N 4 /CNH catalyst include the low amount of catalyst, short reaction time, and solvent-free media (Supplememtary Figures). www.nature.com/scientificreports/  www.nature.com/scientificreports/

Data availability
The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.